目的 探讨载脂蛋白AⅠ(apoAⅠ)对自噬的影响以及与泡沫细胞脂质沉积与凋亡的关系,进一步阐述apoAⅠ抗动脉粥样硬化的机制.方法 将THP-1来源的巨噬细胞随机分为对照组、3-甲基腺嘌呤(3-MA,自噬抑制剂)+apoAⅠ组和apoAⅠ组,加入氧化型低密度脂蛋白(Ox-LDL)并相应干预培养36 h,观察各组细胞中脂滴和自噬小体,检测各组细胞中胆固醇含量、LC3和 Beclin-1的表达水平及凋亡比例.结果 与对照组比较,apoAⅠ能抑制泡沫细胞中脂质沉积,减少细胞中胆固醇含量,抑制细胞的凋亡,上调细胞LC3、Beclin-1的表达(P < 0.01),但予以3-MA后,apoAⅠ的作用被废除(P < 0.05).结论 apoAⅠ通过诱导自噬活性抑制泡沫细胞脂质沉积和凋亡.
Objective To observe the effects of apolipoprotein AⅠ (apoAⅠ) on autophagy,lipid retention,and apoptosis in foam cells, and to explore the anti-atherosclerotic mechanism of apoAⅠ. Methods Macrophages derived from THP-1 cells were randomly divided into the control group,the 3-MA+apoAⅠ group,and the apoAⅠ group. Each group was administered oxidized low-density lipoprotein for 36 hours,then lipid droplets and autophagosomes were observed and cellular cholesterol content was quantified. LC3 and Beclin-1 expression was examined by western blot and the apoptotic ratio determined using flow cytometry. Results Compared with the results of the control group,apoAⅠ treatment inhibited lipid retention and apoptosis in foam cells,decreased cellular cholesterol content,and up-regulated the expression of LC3 and Beclin-1 (P < 0.01). Administration of 3-MA abrogated the effects of apoAⅠ (P < 0.05). Conclusion apoAⅠ inhibits lipid retention and apoptosis in foam cells by inducing autophagy.